DESCRIPTION: (Applicant's Abstract) Cocaine abuse is a major public health problem in the United States, but little is known of the neurochemical pathways that mediate the reinforcing and other properties of cocaine. Nor is there an understanding of the neurochemical changes that accompany cessation of cocaine use following treatment. The brain's endogenous opioid system is known to play an important role in reward mechanisms and our laboratory has demonstrated by the use of C-11 carfentanil and PET scanning that regional brain mu opioid receptors are increased in relation to the degree of cocaine craving. Furthermore, we have demonstrated that following 4 weeks and 90 days monitored abstinence many cocaine addicts normalize or "reset" their increased mu opioid receptors whereas others have persistently elevated levels. We now propose to evaluate the effect of out-patient treatment of cocaine abuse on mu opioid receptors. We will compare 2 forms of treatment: contingent and non-contingent voucher management. In addition to demonstrating a link between treatment outcome and brain function, these studies will determine if measurement of regional brain opioid receptors during the course of therapy predict the long-term treatment outcome with regard to relapse to cocaine use. Results from these investigations will provide vital insights for the development and improvement of behavioral as well as medication treatment of patients with cocaine addiction. We will also separately study and analyze data from men and women patients to explore sex differences in cocaine addiction and the response to treatment. The specific aims of this proposal are: 1) Determine the effect of contingency management versus non-contingent voucher treatment on the change in regional brain mu opioid receptors and cocaine use in patients with cocaine addiction; 2) Determine the relationship between cocaine use and the change in regional brain mu opioid receptors by PET after 4 and 12 weeks of treatment in patients with cocaine addiction; and 3) Determine if there is a relationship between regional brain mu opioid receptors after 12 weeks of treatment and cocaine use after treatment.